Not applicable.
Not applicable.
The invention relates to a reader for microtiter plates or substance chips.
Fluorescence, luminescence, and absorption investigations of huge numbers of very small amounts of samples are necessary in the development of pharmaceutically effective materials, and also in medical molecular diagnosis. Here a high throughput of samples in the measurement is of the greatest importance.
Kinetic measurements are particularly in demand, with time constants which permit a high throughput.
For the preparation of the samples, microtiter plates are available, with small sample holders arranged in a grid pattern in standard configurations with, e.g., 96 or a multiple thereof, e.g., 384 or 1536, sample containers (multi-well microplates). Alternatively, so-called substance chips are also used as sample carriers.
Such a reader is, for example, offered for sale by Molecular Devices Corp., USA, under the designation SPECTRAmax (R) PLUS. A light source and a monochromator are connected by means of 8 optical fibers to 8 mirror optics, each for the transmission illumination of a respective sample holder, and with 8 measuring photodetectors. Eight-fold measurement in parallel is thus possible.
The invention has as its object to provide a reader for microtiter plates or substance chips which makes possible a massively parallel measurement, and thus to very greatly increases the sample throughput, even for kinematic measurements. High efficiency of the light paths, and a compact construction, as simple as possible, are to be attained thereby. A high measurement sensitivity is of course to be insured.
An optical system attains this object. A reader for microtiterplates or substance chips having a plurality of individual sample volumes arranged in a grid pattern dimension, comprising a lens array having a grid pattern dimension that corresponds to the grid pattern dimension of the individual sample volumes of the microtiterplate or substance chip, a detector array, a reflected light illumination device providing illumination light, a telescope between the lens array and the detector array that effects a reduction to match a beam diameter defined by the lens array to the dimensions of the detector array, and a field lens, wherein a reduced image of the microtiterplate or substance chip is formed on the detector array by a system of the lens array, the telescope, and the field lens, so that on the detector array a strict channel separation results between measurement signals arising from the individual sample volumes of the microtiterplate or substance chip, wherein the lens array is achromatized in that each individual lens of the lens array comprises a lens group with achromatic properties, and wherein the illumination light is conducted through the lens array precisely to locations on the microtiterplate or substance chip which are imaged on the detector array attains the object of the invention. The object of the invention is also attained by a reader for microtiterplates or substance chips having a plurality of individual sample volumes arranged in a grid pattern dimension, comprising: a lens array having a grid pattern dimension that corresponds to the grid pattern dimension of the individual sample volumes of the microtiterplate or substance chip, a detector array, a reflected light illumination device providing illumination light, a telescope between the lens array and the detector array that effects a reduction to match a beam diameter defined by the lens array to the dimensions of the detector array, and a field lens, wherein a reduced image of the microtiterplate or substance chip is formed on the detector array by a system of the lens array, the telescope, and the field lens, so that on the detector array a strict channel separation results between measurement signals arising from the individual sample volumes of the microtiterplate or substance chip, the reader comprising a modular construction with the lens array being interchangeable, and wherein several lens arrays are provided, and wherein the individual lenses of different ones of the several lens arrays provide different numerical apertures also attains the object of the invention. For detection, a detector array is provided which is available, for example, as a CCD array. Conventional optics with conventional lenses are combined with lens arrays over the whole cross section. Imaging of the whole sensed object region (microtiter plate) to the correct scale on the CCD array, and also a suitable imaging of the individual wells of the microtiter plate on the CCD array (two different scales), with strict channel separation between the different wells, are thus both attained.
Advantageously, the features stated in the dependent claims are supplementary to this. These include a telescope, which is single-lens over the cross section; a microlens array before the detector array, and the integration of a reflected light illumination. The latter, by double use of the optical elements, results in particularly good efficiency and particularly good noise suppression, in that exactly the sample volume is illuminated which is also sensed by the detection beam path.
A further suppression of interference can be attained with an aperture array.